PPARγ激动剂对小鼠局灶性脑缺血再灌注中性粒细胞浸润和TNF-α表达的影响

The effect of peroxisome proliferator-activated receptor-gamma agonist rosiglitazone on neutrophil infiltration and TNF-α expression after focal cerebral ischemia-reperfusion injury in mice

目的:研究过氧化物酶体增殖物激活受体γ(PPARγ)激动剂罗格列酮对小鼠局灶性脑缺血再灌注中性粒细胞浸润以及TNF-α表达的影响,探讨PPARγ激动剂是否对缺血再灌注脑损伤有保护作用。方法:制作小鼠大脑中动脉阻塞再灌注模型(MCAO/R),随机分为假手术组、模型组和治疗组,分别采用3%氯化三苯四唑(TTC)染色法、神经功能缺损评分法观察PPARγ激动剂对小鼠脑梗死体积和行为学的影响;紫外分光光度法检测脑组织髓过氧化物酶(MPO)活性;免疫组化法观察TNF-α蛋白表达变化。结果:PPARγ激动剂罗格列酮能够显著降低小鼠脑组织的梗死体积(t=7.927,P<0.01)和行为学评分(t=4.540,P<0.01);减轻缺血脑组织MPO活性(t=4.502,P<0.05);减少炎性因子TNF-α蛋白表达水平(t=9.826,P<0.01)。结论:PPARγ激动剂罗格列酮能够减轻脑缺血再灌注脑损伤,其对脑保护作用与炎症抑制有关。

Objective： To investigate the effect of peroxisome proliferator-activated receptor-gamma （PPARγ） agonist, rosiglitazone, on neutrophil infiltration and TNF-α expression after focal cerebral ischemia-reperfusion injury, and whether the PPARγ agonist could has protective againist focal cerebral isehemia-reperfusion injury. Methods： Adult male mice underwent 2 h middle cerebral artery occlusion followed by a 22 h reperfusion （MCAO/R）, were randomly divided into sham group, vehicle group and the rosiglitazone （6 mg/kg） treatment group, TTC staining was adopted to determine the volume of cerebral infarction; The neurological scores were made on Zea Longa 5-point scale; Myeloperoxidase （MPO） activity was measured in brain tissue as an index of neutrophil accumulation; Immunohistochemistry was performed to examine the protein expression of TNF-α. Results： （1） Ischemic size in rosiglitazone group was significantly decreased than that in vehicle group （27.776±5.582 versus 55.396±6.457, t=7.927, P〈0.01）, and rosiglitazone markedly improved neurological function of treated mice than vehicle mice （1.333±0.516 versus 3.500±1.049, t =4.540, P〈0.01 ）. （2） Compared with vehicle group, MPO activity in the rosiglitazonetreated group was significantly lower[（0.052±0.008）U/g versus （0.089±0.012）U/g, t =4.502, P〈0.05]. （3） Consistently, protein expression of TNF-α in treated group were also significantly downregulated than those in vehicle group （t=9.826, P〈0.01 ）. Conclusion： The present study suggests that PPARγ agonist rosiglitazone has neuroprotective properties that are at least partially mediated via anti-inflammatory actions.